Clinical and Investigative Medicine最新文献

Purpose: Obstructive sleep apnea (OSA) leads to endothelial dysfunction and platelet hyperactivity, which arelinked to increased risk of cardiovascular disease and implicated in the development of aspirin resistance. We hypothesized that aspirin resistance is prevalent among OSA patients and aimed to explore effects of continuous positive airway pressure (CPAP) therapy on aspirin responsiveness.Methods: In Phase 1, prevalence of aspirin resistance was determined cross-sectionally in a group of OSA patients (n=59) on daily low-dose aspirin (81 mg) taken before entering the study, for primary or secondary prevention. In Phase 2, aspirin responsiveness before and after initiation of CPAP therapy was compared and stratified by endothelial function in a cohort of aspirin-naïve patients with newly diagnosed OSA (n=18).Results: In Phase 1, prevalence of aspirin resistance was 17%; most patients (56%) were on CPAP therapy. In Phase 2, initiation of CPAP therapy was associated with significant improvement in endothelial function (p=0.03). The mean pre-CPAP aspirin resistance units (ARU) was 569 (SD=75). In subjects with endothelial dysfunction (44%), the mean decrease after initiation of CPAP therapy was 43 ARU (SD=81, p=0.18). In contrast, subjects with normal endothelial function experienced the mean decrease of 8 ARU (SD=116, p=0.83).Conclusion: Aspirin resistance may be prevalent among OSA patients. After initiation of CPAP therapy, we observed a trend towards improvement in aspirin responsiveness among patients with endothelial dysfunction. The role of endothelial dysfunction and aspirin resistance should be explored in further studies that focus on the effect of CPAP on cardiovascular outcomes.

While the separate roles of physicians and scientists are well defined, the role of a physician scientist is broad and variable. In today’s society, physician scientists are seen as a hybrid between the two fields and they are, therefore, expected to be key to the translation of biomedical research into clinical care. This article offers a narrative review on physician scientists and endeavours to answer whether there is an ongoing need for physician scientists today. The historical role of physician scientists is discussed and compared with physician scientists of the 21st century. Fundamental differences and similarities between the separate roles of physicians and scientists are examined as well as the current state of bench to bedside research. Finally, the ability of 21st century physician scientists to impact their respective medical and scientific fields in comparison to non-physician scientists will be discussed. This paper speculates as to why numbers of physician scientists are dwindling and uses the COVID-19 pandemic as an example of rapid translational research. Ultimately, we suggest that physician scientists are important and may have the most impact on their field by working to connect bedside and bench rather than simply working separately in the bedside and bench. To do this, physician scientists may need to lead clinical research teams composed of individuals from diverse training backgrounds.

Purpose: This study aimed to screen hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC)-related feature ribonucleic acids (RNAs) and to establish a prognostic model.Methods: The transcriptome expression data of HBV-associated HCC were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus database. Differential RNAs between HBV-associated HCC and normal controls were identified by a meta-analysis of TCGA, GSE55092 and GSE121248. Weighted gene co-expression network analysis was performed to identify key RNAs and modules. A prognostic score model was established using TCGA as a training set by Cox regression analysis and was validated in E-TABM-36 dataset. Additionally, independent prognostic clinical factors were screened, and the function of lncRNAs waspredicted through Gene Set Enrichment Analysis.Results: A total of 710 consistent differential RNAs between HBV-associated HCC and normal controls were obtained, including five lncRNAs and 705 mRNAs. An optimized combination of six differential RNAs (DSCR4, DBH, ECM1, GDAP1, MATR3 and RFC4) was selected and a prognostic score model was constructed. Kaplan-Meier analysis demonstrated that the prognosis of the high-risk and low-risk groups separated by this model was significantly different in the training set and the validation set. Gene Set Enrichment Analysis showed that the co-expression genes of DSCR4 were significantly correlated with neuroactive ligand receptor interactionpathway.Conclusion: A prognostic model based on DSCR4, DBH, ECM1, GDAP1, MATR3 and RFC4 was developed that can accurately predict the prognosis of patients with HBV-associated HCC. These genes, as well as histologic grade, may serve as independent prognostic factors in HBV-associated HCC.

I hope you’re taking care and found some time to relax this summer. A new semester may mean a big transition—some folks are starting their graduate studies, re-entering clerkship, starting residency or entering a fellowship. For some, there will be little or no change at all; but just a continuation of one of the many phases of the physician-scientist training pathway. Whatever stage you’re at, the Clinical Investigator Trainee Association of Canada (CITAC) community is here to support and advocate for you!

Purpose: The use of intravenous immunoglobulins (IVIG) has increased significantly in the last decade causing challenges for blood suppliers to respond to the demand. Indications for which IVIG infusion should be given to critically ill children remain unclear. The objective of this study is to characterize the epidemiology of IVIG use in this population.Methods: We performed a single-center retrospective cohort study of all patients aged between 3 days and 18 years who received at least one IVIG infusion while hospitalized in the pediatric intensive care unit of the Centre hospitalier universitaire (CHU) Sainte-Justine, Montréal Quebec (Canada) between January 1, 2013 and December 31, 2018.Results: One hundred and seventy-two patients received a total of 342 IVIG infusions over the study period. Most common indications for IVIG infusions were staphylococcal or streptococcal toxic shock syndrome (n=53/342, 15.5%), immunoglobulin replacement in chylothorax (n=37/342, 10.9%), prophylaxis following bone marrow transplantation (n=31/342, 9.1%), myocarditis (n=25/342, 7.3%) and post-solid organ transplant complications (n=21/342, 6.1%). The median dose of IVIG per infusion was 0.95 g/kg (IQR 0.5-1.0) and median number of IVIG infusions per patient was one (IQR: 1-2). Seventy-nine percent of IVIG infusions given were administrated for off-label indications with regards to Health Canada recommendations.Conclusion: This study identified the most common indications for IVIG infusion in critically ill children in a tertiary care pediatric intensive care unit. Given the costs, the known adverse events associated with IVIG and the pressure that blood suppliers are facing to meet the demands, clinical trials are needed to evaluate the efficacy and safety of IVIG in conditions where use is significant.

In this issue, Ryan Kirkpatrick and Gordon Boyd speculated on the reasons for the dwindling number of physician scientists in Canada. To help stimulate discussion on this important issue, Clinical and Investigative Medicine invited two distinguished scientists to present their views on this issue.

Purpose: Infliximab (INX) has been approved for treating Crohn disease (CD) for many years, showing promis-ing efficacy in the clinic. However, the efficacy of the drug and the prognosis of CD vary significantly with dif-ferent locations of disease pathology. This study evaluated the efficacy of INX and prognosis in CD in different locations of disease pathology using systematic meta-analysis.

Methods: We used "Infliximab OR Remicade OR Avakine OR Inflectra OR Renflexis OR Remsima OR IgG1k monoclonal antibody" AND "Crohn's disease OR IBD OR inflammatory bowel disease" as search strategies for searching in PubMed, Wanfang and Embase. A systematic meta-analysis for overall proportions was used to analyze the data.

Results: Twelve studies involving 1,978 patients were included. The results confirmed that treatment with INX led to high clinical remission rates (82%, 95% CI: 64%-92%) and low relapse rates (4%, 95% CI: 2%-9%) in patients with CD. Our results also indicated that use of INX in patients with colon only (L2) CD led to lower clinical remission rates, and use of INX in patients with ileum and colon (L3) CD led to higher relapse rates.

Conclusion: Our findings show different remission rates depending on location of the disease and may be useful for clinicians' choice of therapeutics.

Purpose: Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) overexpression has been reported in various types of cancers. The purpose of this study is to clarify the role of NUCKS, underlying the involvement of non-small-cell lung cancer, in the progression of lung cancer.

Methods: The small interfering ribonucleic acid (siRNA) of NUCKS was transfected into a lung cancer cell line (NCI-H460, A549, NCI-H1299 and NCI-H1975). Functional experiments (MTT assay, Annexin V-FITC/PI double staining assay, colony formation assay, wound healing assay and Transwell assay) were performed to measure the effects of NUCKS on lung cancer cell viability, migration, invasion and apoptosis.

Results: NUCKS was found to be up-regulated in lung cancer cells. Knockdown of NUCKS significantly altered lung cancer cell apoptosis, proliferation colony formation, invasion and migration. Moreover, knockdown of NUCKS attenuated the activation of the PI3K/AKT pathway in lung cancer cells.

Conclusion: NUCKS was overexpressed in lung cancer cells and played an important role in lung cancer by increasing cell growth through the PI3K/AKT signalling pathway. This in vitro study suggested NUCKS should be evaluated in a clinical setting as a novel biomarker and potential therapeutic target for lung cancer.

Purpose: Free wall rupture (FWR) is a lethal complication after acute myocardial infarction; however, the un-derlying mechanisms of FWR are unclear. This study analyzes the relationship between neutrophil counts and FWR following ST-elevation myocardial infarction (STEMI).

Methods: The case group was STEMI patients with FWR and the control group was STEMI patients without FWR (case-control ratio was 1:4). The demographic data, clinical manifestation and laboratory test results were retrospectively collected and analyzed.

Results: Of a total of 6,712 consecutive STEMI patients, 78 patients (1.2%) had FWR. Compared with STEMI patients, patients with FWR were older and more likely to be female with an anterior infarct. White blood cell (WBC) counts were significantly higher in the FWR group. Moreover, we found that the elevated neutrophil counts mainly accounted for the elevated WBC counts. There was also a correlation between the age and neu-trophil counts (P=0.0109); as patient age increased, neutrophil counts decreased (P=0.0387). We also found no correlation between neutrophil counts and the time between myocardial infarction attack and FWR; however, when dividing these patients into FWR ≤48 h after admission to hospital for STEMI and FWR >48 h, there was a significant difference in neutrophil counts (P=0.0196). Furthermore, the results of logistic regression analy-sis showed that increased neutrophil was an independent risk factor for FWR (odds ratio: 2.404, confidence interval: 1.055-5.477).

Conclusion: Elevated neutrophil counts were found to be the main cause of differences in WBC counts be-tween FWR and STEMI. Elevated neutrophil was an independent risk factor for FWR. This study provided clues for further research and development of therapeutics for the prevention of FWR.

Purpose: Hematopoietic cell transplantation (HCT) is associated with significant risk prior to hematopoietic engraftment. Endurance exercise can modify the bone marrow microenvironment, alter hematopoiesis and accelerate hematopoietic regeneration in mouse models of transplantation.

Methods: A systematic review was conducted to clarify the impact of exercise on clinically relevant hemato-logical outcomes in patients following HCT.

Results: A systematic search of the literature identified 13 studies (total of 615 participants; 313 in study arms). Studies included exercise regimens that were primarily low-to-moderate intensity. A total of five studies re-ported on engraftment and length of stay, which were largely unchanged with intervention. Rates of graft-ver-sus host disease were reported in six studies whereas red cell and platelet transfusion needs were reported in four studies, neither of which was different with exercise. Survival was reported in four studies and was significantly improved by exercise in one study.

Conclusions: Exercise in patients receiving HCT appears feasible and safe. Heterogeneity in type and intensity of exercise was observed and few studies examined high intensity exercise. Outcome reporting was inconsis-tent regarding transplant-related outcomes. Standardized hematological outcome measures are needed to clarify the impact of higher intensity exercise on HCT.